Official Title: “Clinical Trial of Gabapentin to Improve Postoperative Pain in Surgical Patients”

This will be a double blind, placebo-controlled study of patients ≥45 years of age undergoing surgery of the spine at the University of California, San Francisco (UCSF) Medical Center.

Intraoperative anesthetic and postoperative pain management will be standardized. Patients will be randomized to receive either placebo or gabapentin preoperatively, and continued postoperatively until discharge. Intraoperative anesthetic and other postoperative pain management strategies will be standardized. Postoperative delirium will be measured using structured interviews. Cognitive function will be measured using a battery of neurocognitive tests pre- and post-operatively. Using an intention to treat strategy, we, the researchers at UCSF, will compare the amount of postoperative pain, narcotic requirements, and postoperative delirium and cognitive dysfunction between the two groups.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2012

Postoperative delirium is a common condition, occurring in 10-70% of surgical patients after major surgery. To date, few studies have examined events in the postoperative period as contributing factors to postoperative delirium. We recently completed a study in over 500 geriatric surgical patients to examine whether the mode of postoperative analgesia delivery, medication types, and the severity of postoperative pain may impact the occurrence of postoperative delirium. In this study, 46% of patients developed postoperative delirium on either the first or second postoperative day. By multivariate logistic regression, variables which had independent association with postoperative delirium included age ≥80 years, moderate to severe preoperative resting pain, and increased level of resting pain postoperatively in comparison with preoperative baseline. When the analysis was focused on patients who used Patient Controlled Analgesia (PCA) alone for postoperative pain control, the amount of narcotic used (hydromorphone) was significantly higher in those with postoperative delirium as compared to those without, suggesting that inadequate pain control and/or the central effects of opioids may be associated with postoperative delirium. Since increasing the doses of opioids in the elderly patients will likely lead to unwanted side effects such as respiratory depression, the addition of a non-opioid agent may result in a narcotic-sparing effect, and also reducing pain postoperatively.

Gabapentin is a structural analog of gamma-amino butyric acid, and has been used as an anti-convulsant and anti-nociceptive drug. It is not metabolized in humans (therefore no hepatic enzyme induction), and is eliminated from the body by renal clearance. In animal studies, gabapentin has been demonstrated to be effective in reducing both allodynia and hyperalgesia, and may have selective effect on the nociceptive process involved in central sensitization. Gabapentin has been successfully used in the treatment of neuropathic pain and other painful conditions. Recently, there is substantial evidence to suggest that gabapentin also may be useful in the treatment of postoperative pain. To date, there have been nine randomized clinical trials of gabapentin versus placebo including a total of over 700 patients. Taken together, these studies reported that gabapentin given perioperatively significantly reduced postoperative analgesic requirements, and had minimum side effects.

The only reported significant side effects in these trials were mild sedation in two studies.

In patients with epilepsy, gabapentin can be introduced at therapeutic doses, and presents no safety or serious side effect issues. Since gabapentin has negligible protein binding, it has no interactions with other medications. It is recommended that metabolic and laboratory monitoring is not necessary, and excellent cognitive profile is evident. At UCSF, gabapentin has been used safely in a relatively large number of patients on an empiric bases in the postoperative period, typically in surgical patients with substantial chronic pain, and more recently, in patients who have undergone spinal surgery as an adjuvant agent to narcotics to relieve postoperative radicular pain (personal communication with Peter Koo, Clinical Pharmacist at UCSF). Typically, patients are started on gabapentin 300 mg po TID on the first day, rapidly escalating to 600 mg TID on the second day, and finally to 900 mg TID the third day until discharge. The UCSF experience suggests that gabapentin is well tolerated with minimal side effects.

Hypothesis

We hypothesize that intensive pain management postoperatively using an adjuvant agent, gabapentin, will lead to a decrease in the amount of postoperative pain experienced, thereby resulting in a decrease in the incidence of postoperative delirium in elderly patients undergoing surgery of the spine.

Aims

1. To compare the amount of postoperative pain between the placebo vs. the gabapentin groups

2. To compare the amount of narcotic used postoperatively between the placebo vs. the gabapentin groups

3. To compare the incidence of postoperative delirium and cognitive dysfunction between the placebo vs. the gabapentin groups

Objectives

1. The broad overall goal is to identify the pathophysiology of postoperative delirium and cognitive dysfunction in older patients

2. To determine whether optimization of postoperative pain control will reduce the incidence of postoperative delirium and cognitive dysfunction

Intervention(s) in this Clinical Trial

• Drug: Gabapentin
  • gabapentin adjusted for renal clearance given preoperatively and also the first three postoperative days

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: Gabapentin
  • already described

Primary Measures

• Postoperative opioids doses and Visual Analogue Scale (VAS) pain scores
  • Time Frame: postoperative days 1, 2 and 3
    Safety Issue?: No

Secondary Measures

• Postoperative rates of delirium and cognitive decline
  • Time Frame: postoperative days 1, 2 and 3
    Safety Issue?: Yes

Inclusion Criteria:

• Male or female ≥45 years of age undergoing surgery involving the spine, hip or knee replacement.
• English speaking.
• Anticipated to stay in the hospital for at least 48 hours.

Exclusion Criteria:

• Patients who take gabapentin preoperatively, or have known sensitivity to the drug, or those unable to be randomized to receive gabapentin.
• Subjects who are unable to provide informed consent.
• Patients with a history of narcotic tolerance.
• Patients with planned two stage spinal procedures (anterior-posterior spinal fusion to be done on two separate days).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 65 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of California, San Francisco

Overall Clinical Trial Officials and Contacts

Jacqueline M Leung, MD, MPH Principal Investigator University of California, San Francisco, CA, USA  

Overall Contact: Jacqueline M Leung, MD, MPH 415-476-0711 leungj@anesthesia.ucsf.edu

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00221338

Study ID Number: H5636-26795-01

ClinicalTrials.gov Identifier: NCT00221338

Health Authority: United States: Institutional Review Board